全反式维甲酸联合阿帕替尼抑制口腔鳞癌细胞增殖体外研究

口腔生物医学 ›› 2022, Vol. 13 ›› Issue (1): 15-19.

全反式维甲酸联合阿帕替尼抑制口腔鳞癌细胞增殖体外研究

潘新华,李烿烿,叶露露,朱国培

海交通大学医学院附属第九人民医院

收稿日期:2021-08-20 修回日期:2021-12-02 出版日期:2022-03-25 发布日期:2022-03-21
通讯作者: 朱国培 E-mail:antica@gmail.com
基金资助:
ALCAM上调ABCB1转运体介导肿瘤干细胞耐药的分子机制

In vitro Study on the Inhibition of oral squamous cell carcinoma Induced by All-Trans Retinoic Acid and Apatinib

Received:2021-08-20 Revised:2021-12-02 Online:2022-03-25 Published:2022-03-21

摘要/Abstract

摘要： 目的：观察和分析全反式维甲酸（ATRA）联合阿帕替尼对口腔鳞癌细胞的增殖抑制作用。方法：实验分为对照组、ATRA组、阿帕替尼组及联合用药组，利用MTT法检测ATRA联合阿帕替尼对口腔鳞癌细胞CAL27及HN4增殖的影响；倒置显微镜观察两药联用对口腔鳞癌细胞形态的影响；利用实时定量RT-PCR法检测肿瘤细胞角蛋白KRT1、KRT10和干性相关基因及IGF1/IGF1R信号通路相关基因的表达水平。结果：ATRA、阿帕替尼单药使用均抑制肿瘤细胞增殖，两药联用组细胞增殖抑制率明显高于单药处理组（P<0.01），且两药联用在不同时间均对口腔鳞癌细胞增殖抑制作用呈现相加或协同作用。两药联用影响口腔鳞癌细胞的形态变化，上调KRT1、KRT10表达，促进其老化。两药联用抑制CAL27细胞肿瘤干性基因的表达，消除肿瘤细胞干性（P<0.05）。两药联用促进IGFBP3表达，抑制IGF1/IGF1R信号通路活性。结论：ATRA联合阿帕替尼通过促进细胞老化，影响细胞干性，抑制口腔鳞癌细胞增殖。

Abstract: Objective:To investigate the effects of all-trans retinoic acid(ATRA) and Apatinib on the proliferation of oral squamous cell carcinoma(OSCC). Methods:The effect of ATRA and Apatinib on the proliferation was detected by MTT assay in CAL27 and HN4 cell. The morphology changes of cells were observed by inverted microscope. Relative mRNA expression of KRT1, KRT10 and the stemness genes and IGF1/IGF1R signaling pathway related genes in OSCC were compared by quantitative real time RT-PCR. Results: ATRA and Apatinib inhibited OSCC proliferation, while the cell growth inhibition in ATRA combined with Apatinib group was more significantly than ATRA group or Apatinib group(P<0.05). A series of cell morphological changes was observed in the combined treatment group. ATRA combined with Apatinib significantly upregulated the expression of KRT1 and KRT10, promoting cell senescence(P<0.05). ATRA combined with Apatinib decreased the expression of stemness genes, eliminating the stemness of OSCC, and inhibited the activity of IGF1/IGF1R signaling pathway (P<0.05). Conclusions:The double roles of ATRA combined with Apatinib in OSCC: promoting cell senescence and eliminating the stemness of OSCC stem cell and thus suppressing cell proliferation.

中图分类号:

R739.8

潘新华李烿烿叶露露朱国培. 全反式维甲酸联合阿帕替尼抑制口腔鳞癌细胞增殖体外研究[J]. 口腔生物医学, 2022, 13(1): 15-19.

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